Central Nervous System Aspergillosis in an Immunocompetent Patient

Aspergillus sp. is a fungus that is very common in nature and may cause invasive disease with high mortality, especially in immunosuppressed patients. Here we present a case of central nervous system (CNS) aspergillosis in a previously healthy immunocompetent patient. A 23-year-old female was admitted to hospital with the complaints of headache, blurred vision, and double vision. In her cranial magnetic resonance imaging, abscess and paranchymal edema were observed in the left frontal lobe, and biopsy was performed with endoscopic nasal operation. The pathology result was consistent with aspergillus infection. It should be remembered that although CNS aspergillosis generally occurs in immunosuppressed patients, it may also rarely be diagnosed in immunocompetent individuals. Copyright © 2011Kose et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction Aspergillus sp. is a fungus that is very common in nature and may cause an invasive disease with high case fatality rate, especially in immunosuppressive patients [1]. Major risk factors for aspergillus infection include neutropenia and corticosteroid use [2]. Central nervous system (CNS) aspergillus is very rare in immunocompetent patients. The infections mostly occur through hematogenous dissemination from a focus, such as lung infection, or rarely through direct extension from the paranasal sinuses [3,4]. The most common symptoms include progressive headache, weakness or paraesthesia, and altered mental state [5]. The diagnosis and treatment of invasive CNS aspergillosis is very difficult. Early diagnosis is important for a successful treatment. Here we present a case of CNS aspergillosis in a previously healthy immunocompetent patient.


Introduction
Aspergillus sp. is a fungus that is very common in nature and may cause an invasive disease with high case fatality rate, especially in immunosuppressive patients [1].Major risk factors for aspergillus infection include neutropenia and corticosteroid use [2].Central nervous system (CNS) aspergillus is very rare in immunocompetent patients.The infections mostly occur through hematogenous dissemination from a focus, such as lung infection, or rarely through direct extension from the paranasal sinuses [3,4].The most common symptoms include progressive headache, weakness or paraesthesia, and altered mental state [5].The diagnosis and treatment of invasive CNS aspergillosis is very difficult.Early diagnosis is important for a successful treatment.Here we present a case of CNS aspergillosis in a previously healthy immunocompetent patient.

Case report
A 23-year-old female was admitted to hospital with the complaints of headache persisting for approximately six months.She stated that the complaints of blurred vision and double vision were added recently.She had no known disease and no apparent immune deficiencies.No pathology was found in her physical examination.Initial neurologic examination did not reveal any abnormalities.Her laboratory results were as follows: white cell count, 11.000/µl; sedimentation rate, C-reactive protein, peripheral smear and biochemical tests were all in normal range.HIV test was negative; IgG and subtypes and CD4 and CD8 counts were normal.In her cranial magnetic resonance imaging (MRI), abscess surrounded by severe paranchymal edema was observed in the left frontal lobe (Figure 1).A biopsy was performed with endoscopic nasal operation.The biopsy material showed inflammatory granulation tissue and microabscesses containing a large number of hyphae with 45 degree angulations and spores.The pathology result was consistent with aspergillus infection.Voriconazole (6 mg per kilogram intravenously twice a day on day 1, followed by 4 mg per kilogram intravenously twice daily) was initiated.The patient was operated and the lesion was resected.After a year of treatment, voriconazole was discontinued since the lesion totally dissapeared on MRI without any complications.

Discussion
The occurrence of fungal infections increased in the last decade due to the increase in the life span of the immunosuppressive patients [6].Fungal infections of the central nervous system mostly result from systemic circulation secondary to lung infection, and may result from the direct extension from the paranasal sinuses [7].Most fungi cause basal meningitis or intraparenchymal abscesses; however, direct extension from the cribriform plate can cause necrohemorrhagic lesions in the base of the frontal lobe.A study performed by Murthy et al. reported that central nervous system aspergillosis resulted from the direct extension from the paranasal sinuses in 76% of cases [8].We consider that the CNS aspergillus infection in our patient resulted from neighboring tissues following chronic sinusitis even though the patient had no immunosuppressive condition.
Aspergillus infection of paranasal sinuses is rare.However, the number of reported cases increased significantly in the last decade.Aspergilloma was identified as an etiological agent in 10% of the patients with chronic sinusitis, and it was observed more in women (64%) than in men.Infections are often confined to a single sinus and generally maxillary was the most involved sinus followed by sphenoidal sinus infections [9].The infection can manifest especially in patients who have undergone bone marrow or solid organ transplantations, in immune-compromised patients with hematological malignancies and acquired immune deficiency, and rarely in immunocompetent patients, as in our case [10].The clinical presentation in immunosuppressed patients is non-specific and mild, and symptoms include headache as in sinusitis, rhinorrhea, nasal obstruction, and fever.The diagnosis is difficult in asymptomatic infections.Rapid infiltration to neighbor tissues such as the orbital and frontal areas is typical, and computed tomography (CT) is recommended to show the bone destruction.Magnetic resonance imaging (MRI) is generally recommended for meningeal or intraparenchymal involvement and for the early diagnosis of intracranial vascular occlusion.The definitive diagnosis is made with histological tests.The hyphae appearance with branches of 45 degrees is a typical and specific finding for aspergillus infection [11].A soft tissue density that forms bone destruction in the left olphactory sulcus was observed by paranasal sinus CT in our case.The commonly recommended treatment is voriconazole for CNS aspergillus infection.Case fatality rates range between 28% to 86%, despite high-dose antifungal treatment and radical surgery.The other treatments are amphotericin-B, itraconazole, caspofungin and posakonasole.Amphotericin-B is one of the preferred antifungals; however, its therapeutic use is limited because of its adverse effects, including renal and hepatic toxicity, anemia, fever and electrolyte abnormalities [12].In a study performed by Herbrecht et al. (2002), voriconazole and amphotericin-B were compared in invasive aspergillus.In the 12th week of therapy, the partial or complete success rate was 53% for voriconazole and 32% for amphotericin-B.Based on these results, many authors accepted that efficacy and survival rate is higher with voriconazole in invasive aspergillus [13].It should be remembered that although CNS aspergillosis generally occurs in immunosuppressed patients (such as cancer patients, organ transplant recipients, diabetes mellitus), it may also rarely occur in immunocompetent individuals.

Figure 1 .
Figure 1.MRI showing abscess surrounded by severe paranchymal edema in the left frontal lobe.